This Article Full Text Full Text (PDF) Online Supplement All Versions of this Article: 200612-1890OCv1 177/2/208    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lee, Y.-M. Articles by Dakhama, A. Search for Related Content PubMed PubMed Citation Articles by Lee, Y.-M. Articles by Dakhama, A.

IFN- Production during Initial Infection Determines the Outcome of Reinfection with Respiratory Syncytial Virus

¹ Division of Cell Biology, Department of Pediatrics, National Jewish Medical and Research Center, Denver, Colorado

Correspondence and requests for reprints should be addressed to Azzeddine Dakhama, Ph.D., Division of Cell Biology, Department of Pediatrics, National Jewish Medical and Research Center, Denver, CO 80206. E-mail: dakhamaa{at}njc.org

Rationale: Severe respiratory syncytial virus (RSV) bronchiolitis has been associated with deficient IFN- production in humans, but the role of this cytokine in determining the outcome of reinfection is unknown.

Objectives: To define the role of IFN- in the development of RSV-mediated airway hyperresponsiveness (AHR) and lung histopathology in mice.

Methods: Wild-type (WT) and IFN- knockout mice were infected with RSV in the newborn or weaning stages and reinfected 5 weeks later. Airway responses were assessed on Day 6 after the primary or secondary infection.

Measurements and Main Results: Both WT and IFN- knockout mice developed similar levels of AHR and airway inflammation after primary infection. After reinfection, IFN- knockout mice, but not WT mice, developed AHR, airway eosinophilia, and mucus hyperproduction. Intranasal administration of IFN- during primary infection but not during reinfection prevented the development of these altered airway responses on reinfection in IFN- knockout mice. Adoptive transfer of WT T cells into IFN- knockout mice before primary infection restored IFN- production in the lungs and prevented the development of altered airway responses on reinfection. Treatment of mice with IFN- during primary neonatal infection prevented the enhancement of AHR and the development of airway eosinophilia and mucus hyperproduction on reinfection.

Conclusions: IFN- production during primary RSV infection is critical to the development of protection against AHR and lung histopathology on reinfection. Provision of IFN- during primary infection in infancy may be a potential therapeutic approach to alter the course of RSV-mediated long-term sequelae.

Key Words: respiratory syncytial virus • interferon- • asthma • airway hyperresponsiveness • mice

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject Deficient IFN- production has been associated with respiratory syncytial virus (RSV) bronchiolitis. However, the role of IFN- in determining the outcome of reinfection with RSV remains unknown. What This Study Adds to the Field IFN- plays a critical role during initial infection that determines the outcome of reinfection with RSV. Provision of IFN- may interfere with the development of altered airway responses to reinfection in children.

 

This article has been cited by other articles:

				S. S. Mohapatra and S. Boyapalle Epidemiologic, Experimental, and Clinical Links between Respiratory Syncytial Virus Infection and Asthma Clin. Microbiol. Rev., July 1, 2008; 21(3): 495 - 504. [Abstract] [Full Text] [PDF]

				J. S. Tregoning, Y. Yamaguchi, J. Harker, B. Wang, and P. J. M. Openshaw The Role of T Cells in the Enhancement of Respiratory Syncytial Virus Infection Severity during Adult Reinfection of Neonatally Sensitized Mice J. Virol., April 15, 2008; 82(8): 4115 - 4124. [Abstract] [Full Text] [PDF]